The role of autoantibodies in the pathogenesis of human demyelinating diseases of the central nervous system (CNS) is an important unresolved issue in the field of neuroimmunology. In animal models, autoantibodies that recognize epitopes located on the surface of myelin or myelin-producing oligodendrocytes can enhance demyelination (Linington et al., Am. J. Pathol., 1988, 130(3):443-54; Schluesener et al., J. Immunol., 1987, 139(12):4016-21).
Injection of a monoclonal antibody (mAb 8-18C5) against myelin oligodendrocyte glycoprotein (MOG) into mice or rats with mild experimental autoimmune encephalomyelitis (EAE) induces severe demyelination, but does not induce any disease in healthy animals because the antibody does not gain access to the CNS parenchyma (Linington et al., Am. J. Pathol. 1988; 130(3):443-54; Schluesener et al., J. Immunol. 1987; 139(12):4016-21). MOG is a relatively minor protein component of myelin, but is localized on the outer surface of the multi-lamellar myelin structure, while more abundant antigens such as myelin basic protein (MBP) are inaccessible to antibodies in intact myelin (Linington et al., Am. J. Pathol. 1988; 130(3):443-54).
In the marmoset primate model of EAE, immunization with MOG induces a chronic demyelinating disease with pathological features reminiscent of multiple sclerosis (MS) (Genain et al., J. Clin. Invest. 1995; 96(6):2966-74). However, in mouse models, severe demyelination is observed even in the apparent absence of antibodies and B cells (Hjelmstrom et al., J. Immunol. 1998; 161(9):4480-3), indicating that autoantibodies are not required for demyelination in all species.
These studies in animal models have demonstrated the demyelinating potential of autoantibodies to myelin surface proteins, but their role in the pathogenesis of human diseases is far less certain. Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) are the most common demyelinating diseases in adults and children, respectively.